Although aging may reflect, in part, the outcome of environmental stresses on cells and tissues, a question of major interest is whether some inherent physiological deterioration underlies the environmental effects. The human diploid cell lines and the virus-transformed cultures derived from them provide an avenue of approach to this question. Cultures of the former have a finite life span in terms of the total number of successive generations they can undergo. The latter cells have an indeterminate life span. The subject of this proposal is the mechanism of control of senescence and proliferation. We are interested in defining the successive procession of events making up the phenomenon of cellular senescence in terms of quantitative biochemical relationships. Our objective is to examine, in a systematic way, using young, old and transformed diploid cells, aspects of transcription, translation, protein function, the structure-function relationships of various organelles and the effects of genetic alteration on life span. We will first describe, in molecular terms, the changes which occur during cell aging and during and after transformation. Based on these studies we will then analyze the key reactions involved in these processes.